presents

Symposium

Wednesday, May 17, 2006
Raritan Valley Community College
North Branch, New Jersey
(Directions)

Registration
Please use the Registration Form Below

The Visions Symposium hosts pioneers in their respective areas of expertise
whose work is considered visionary in the field of chemistry.

PROGRAM
8:30	Registration and Continental Breakfast
9:45	Introductory Remarks
10:00	Philip Baran Scripps Research Institute, San Deigo "The Catalytic Cycle of Discovery in Total Synthesis" The practice of total synthesis is a tried and true means to harvest the infinite chemical wisdom found in natural products. Selected studies from our lab will be presented on the total synthesis of complex heterocyclic natural products (see Figure below for selected targets).
11:00	Christopher A. Lipinski Formerly with Pfizer "Drug-like or Tool-like compounds: Why does it matter in biological screening?" In discovery of biologically active compounds the nature of the screening library is extremely important. Is the goal to discover a chemical tool to “validate” a biological target? Or is the goal to discover a starting point for drug discovery? These are both important goals but they require distinctly different types of screening libraries. As academics and organizations unfamiliar with drug discovery start screening efforts, failure to understand the difference between drug-like and tool-like can lead to disastrous consequences. Regardless of the goal, the current politically correct mantra of screening diverse compounds is, in my opinion, the worst possible way to discover a starting point. Truly diverse libraries are experimentally inaccessible and biological activity is not uniformly and randomly distributed throughout chemical space. The typical achiral medicinal chemistry compound can be viewed as a “somewhat slippery” chemical probe that searches a fairly large chemical space. This type of probe works best by re-using favored motifs and is most successful against families of related targets. From the work in the area of drug repurposing we know that roughly 10% of drugs might have useful unanticipated therapeutic activity. By contrast, natural products can be viewed as “more precise” chemical probes from a distinctly different chemical tool kit that search across a limited chemical space. Natural products are successful primarily because an evolutionary high throughput screening has been occurring for millennia. Diversity oriented synthesis efficiently produces complex chemical structures more akin to natural products than to typical combinatorial chemistry compounds. Like natural products the chemistry space searched is smaller. The success is better when the target is phenotypic rather than mechanistic. The phenotypic screen by greatly expanding the target opportunity space compensates for the restricted ligand chemistry search space. Another politically correct misperception is that the genomics revolution has produced thousands of targets for orally active medicines. Although there might be thousands of proteins capable of binding low molecular weight compounds very few of these will be capable of becoming drugs. The proof of this is the high failure rate in the late stages of clinical studies. Biological pathways tend to be robust and blocking a single pathway step may not do anything useful in human medicine. Usually one thinks of the effect of a drug on the body, but often equally important is the body reaction to the drug. This leads to the puzzle that not infrequently it is unclear whether an antagonist or agonist might be required in a medicinally useful compound.
12:00 pm	Lunch Break
1:30	Viresh Rawal University of Chicago "Asymmetric Catalysis of Chemical Reactions Promoted by Hydrogen Bond Activation" The bare hydrogen atom-a proton-functioning in the Bronsted-Lowry sense, is the most commonly used catalyst for promoting chemical reactions. In contrast, the Lewis acid property of the hydrogen atom, most evident in hydrogen bonds, has been little utilized for catalysis. Indeed, in contemporary organic synthesis, especially for asymmetric reactions, the notion of Lewis acid catalysis has become synonymous with metal-based catalysis. Hydrogen bonds, while of central importance for the organization and function of large biomolecules, have played at best a minor role in the promotion of chemical reactions. Only a handful of reports describe the successful use of hydrogen bonds for non-enzymatic asymmetric catalysis. In this presentation I will summarize our work on the use of chiral hydrogen bond donors for the promotion of asymmetric reaction.
2:30	Amos B Smith III University of Pennsylvania "Evolution of the Petasis-Ferrier Union/Rearrangement Tactic In Total Synthesis" The tetrahydropyran ring with substituents oriented 2,6-cis often comprises the signature element found in a variety of biologically active natural products. In 1999, we disclosed a three-step extension of what we termed the Petasis-Ferrier union/rearrangement tactic to construct the two 2,6-cis-substituted tetrahydropyran rings found in (+)-phorboxazole A. More recently, we have demonstrated the power of this synthetic tactic in studies directed toward the total syntheses of a number of natural products, including: (+)- zampanolide, (+)-dactylolide, (+)-spongistatin 1, (-)-endomycin, (+)-sorangicin, okilactomycin, chrolactomycin, and (-)-clavosolide C. The evolution of the Petasis- Ferrier union/rearrangement tactic, as well as current synthetic applications will be presented. • Smith, A.B., III; Verhoest, P.R.; Minbiole, K.P.; Lim, J.J. Org. Lett. 1999, 1, 909 • Smith, A.B,, III; Minbiole, K.P.; Verhoest, P.R.; Beauchamp, T.J. Org. Lett. 1999, 1, 913
3:30	Coffee Break
3:50	Tony Zhang Eli Lilly & Company "The Integration of Business and Sciences for Pharmaceutical Chemistry: Logic and Logistic" Synthetic processes developed for pharmaceuticals are meant to be repeated many times with a high degree of predictability and consistency. Case studies of synthetic route development for several drug candidates will be given to demonstrate the importance of seamlessly integrating business considerations in the design stage for the optimum economical outcome in a long run. The value of leveraging logistical advantages will also be illustrated.
4:50	Closing Remarks
5:00	Evening Cocktail Reception

No fee associated with attendance and registration.
Voluntary donations to the RVCC Science Department will be accepted at the door.

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We ask that if you register early and later find that you cannot attend to please revisit this form and cancel your registration.
The event will include a continental breakfast, refreshment break, luncheon mixer and an evening mixer reception (not full dinner).

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Sponsored by Sanofi-Aventis Science & Medical Affairs Division